Objective: Proliferative vitreoretinopathy (PVR) is still one of the most serious complications of rhegmatogenous retinal detachment (RRD) because there is no effective treatment or prophylaxis. Tumor necrosis factor α (TNFα) has been implicated in the development of PVR. Thus, the blockade of this factor could reduce or prevent the onset of PVR. However, systemic treatment with anti-TNFα has some risks and side effects, and the use of these drugs in this situation is not yet justified. Therefore we sought an indirect approach to determine if systemic anti-TNFα provided any protection against the development of PVR after RRD surgery. We attempted to estimate the rate of RRD and PVR in patients who were treated systemically with anti-TNFα drugs because of autoimmune diseases and who also had surgically-treated RRD.Methods: Nine centers participated in this retrospective, observational study of cases and controls. Two different approaches were used to find cases and controls. The records at five clinical centers of patients who were under anti-TNFα treatment for chronic inflammatory systemic diseases between January 2004 and 2014 were reviewed to determine how many developed RRD. Additionally, the records in eight clinical centers of patients who underwent RRD surgery during this same period were reviewed to determine the numbers who were simultaneously receiving anti-TNFα treatment. Cases included patients treated with anti-TNFα treatment whereas controls were those who were not under anti-TNFα treatment. Both patients and controls had systemic inflammatory disease. The main outcome measure was development of PVR after RRD surgery at three months follow-up.Results: A total of 8,017 medical records from nine different centers were reviewed. Among the 1,884 patients with anti-TNFα treatment and 6,133 patients operated for primary RRD, only 3 controls and 1 case were identified.Conclusions: An insufficient number of patients were identified to allow any valid conclusion regarding our hypothesis that systemic anti-TNFα therapy could reduce the onset of PVR after RRD surgery. Nevertheless, this indirect approach could be useful for future research in PVR prevention.